13C, 25Mg, and 43Ca Solid-State NMR for the Purpose of Dolomitic Marbles Provenance Elucidation.

The study of the provenance of dolomitic marble artefacts has become relevant since it was discovered that quarries of this marble other than that of Cape-Vathy located on the island of Thasos have been exploited since Antiquity. To improve our knowledge about the provenance of materials and the extent of their dispersion, multiple archaeometric studies were performed in the past including isotope analyses, petrography, cathodoluminescence, and elemental analyses. In the present work, solid-state nuclear magnetic resonance (NMR) spectroscopy has been added to this panel of techniques. NMR allows the characterization of the material at a molecular level by looking at different nuclei: carbon, magnesium, and calcium. Statistical analysis of the data collected on both quarry samples and archaeologic items was also implemented and clearly demonstrates the efficiency of a holistic approach for provenance elucidation. Finally, the first 25Mg NMR tests have shown the potential of this technique to discriminate between dolomitic marbles of different provenance. The results are discussed in terms of their historical meaning and illustrate the exploitation of sources of dolomitic marbles other than the Greek Thasos source.

The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial.

BACKGROUND: Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) trial, which compares the use of angiogenic factors and Doppler to manage small fetuses at term. OBJECTIVE: The primary objective is to demonstrate that classification based on angiogenic factors is not inferior to estimated fetal weight and Doppler at detecting fetuses at risk of adverse perinatal outcomes. METHODS: This is a multicenter, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1030 singleton pregnancies with an estimated fetal weight ≤10th percentile at 36+0 to 37+6 weeks+days will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio ≥38 will be classified as having fetal growth restriction; otherwise, they will be classified as being small for gestational age. In both arms, the fetal growth restriction group will be delivered at ≥37 weeks and the small for gestational age group at ≥40 weeks. We will assess differences between the groups by calculating the relative risk, the absolute difference between incidences, and their 95% CIs. RESULTS: Recruitment for this study started on September 28, 2020. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences in early 2023. CONCLUSIONS: The angiogenic factor-based protocol may reduce the number of pregnancies classified as having fetal growth restriction without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities. TRIAL REGISTRATION: ClinicalTrials.gov NCT04502823; https://clinicaltrials.gov/ct2/show/NCT04502823. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37452.

Evolving mortality and clinical outcomes of hospitalized subjects during successive COVID-19 waves in Catalonia, Spain.

BACKGROUND: The changes in shield strategies, treatments, emergence variants, and healthcare pathways might shift the profile and outcome of patients hospitalized with COVID-19 in successive waves of the outbreak. METHODS: We retrospectively analysed the characteristics and in-hospital outcomes of all patients admitted with COVID-19 in eight university hospitals of Catalonia (North-East Spain) between Feb 28, 2020 and Feb 28, 2021. Using a 7-joinpoint regression analysis, we split admissions into four waves. The main hospital outcomes included 30-day mortality and admission to intensive care unit (ICU). FINDINGS: The analysis included 17,027 subjects admitted during the first wave (6800; 39.9%), summer wave (1807; 10.6%), second wave (3804; 22.3%), and third wave (4616; 27.1%). The highest 30-day mortality rate was reported during the first wave (17%) and decreased afterwards, remaining stable at 13% in the second and third waves (overall 30% reduction); the lowest mortality was reported during the summer wave (8%, 50% reduction). ICU admission became progressively more frequent during successive waves. In Cox regression analysis, the main factors contributing to differences in 30-day mortality were the epidemic wave, followed by gender, age, diabetes, chronic kidney disease, and neoplasms. INTERPRETATION: Although in-hospital COVID-19 mortality remains high, it decreased substantially after the first wave and is highly dependent of patient's characteristics and ICU availability. Highest mortality reductions occurred during a wave characterized by younger individuals, an increasingly frequent scenario as vaccination campaigns progress. FUNDING: This work did not receive specific funding.

Emergency Department capacity to initiate thromboprophylaxis in patients with atrial fibrillation and thrombotic risk after discharge: URGFAICS cohort analysis.

Atrial fibrillation (AF) is the most prevalent heart rhythm disorder in the general population. Stroke prevention is one of the leading management objectives in the treatment of AF patients. The variables associated with the non-initiation of thromboprophylaxis in patients with thrombotic risk consulting for an episode of AF in Emergency Departments (ED) were investigated. This was a multipurpose, analytical, non-interventionist, multicenter Spanish study with a prospective 30-day follow-up. All patients ≥ 18 years of age consulting to the ED for the casual finding of AF in an electrocardiogram (ECG) performed 12 h prior to the consultation or with symptoms related to AF were enrolled from September 1, 2016 to February 28, 2017. Patients not previously received thromboprophylaxis were selected. Multivariate analysis was performed to calculate the odds ratio (OR) and the 95% confidence interval (CI). A total of 634 patients, not received thromboprophylaxis and at high thrombotic risk, were included. Of these, 251 (39.6%) did not receive thromboprophylaxis at ED discharge. In the multivariate analysis, non-initiation of anticoagulation at discharge from the ED was mostly related to cognitive impairment (OR 3.95; (95% CI 2.02-7.72), cancer history (OR 2.12; (95%CI 1.18-3.81), AF duration < 48 h (OR 2.49; (95% CI 1.48-4.21) and patients with re-establishment of sinus rhythm (OR 3.65; (95% CI 1.47-9.06). Reinforcement of the use of CHA2DS2-VASC as a stroke risk scale and empowerment of ED physicians is a must to improve this gap in care.

Long Covid-19: Proposed Primary Care Clinical Guidelines for Diagnosis and Disease Management.

Long COVID-19 may be defined as patients who, four weeks after the diagnosis of SARS-Cov-2 infection, continue to have signs and symptoms not explainable by other causes. The estimated frequency is around 10% and signs and symptoms may last for months. The main long-term manifestations observed in other coronaviruses (Severe Acute Respiratory Syndrome (SARS), Middle East respiratory syndrome (MERS)) are very similar to and have clear clinical parallels with SARS-CoV-2: mainly respiratory, musculoskeletal, and neuropsychiatric. The growing number of patients worldwide will have an impact on health systems. Therefore, the main objective of these clinical practice guidelines is to identify patients with signs and symptoms of long COVID-19 in primary care through a protocolized diagnostic process that studies possible etiologies and establishes an accurate differential diagnosis. The guidelines have been developed pragmatically by compiling the few studies published so far on long COVID-19, editorials and expert opinions, press releases, and the authors' clinical experience. Patients with long COVID-19 should be managed using structured primary care visits based on the time from diagnosis of SARS-CoV-2 infection. Based on the current limited evidence, disease management of long COVID-19 signs and symptoms will require a holistic, longitudinal follow up in primary care, multidisciplinary rehabilitation services, and the empowerment of affected patient groups.

[HOSPITALS AS PROMOTERS OF SMOKELESS SPACES: STRATEGIES AIMED AT SMOKING CONTROL] / El hospital como centro promotor de espacios sin humo: estrategias dirigidas al control del tabaquismo.

The objective of this study was to describe the measures introduced at the Hospital Germans Trias i Pujol, Barcelona, aimed at achieving a smoke-free environment, and encouraging research, training, and clinical approaches with respect to smoking. The experience gained as a center attached to the Catalan Network of Smokeless Hospitals since 2002 shows that preventing and controlling smoking requires a specific agenda developed by a competent committee comprising workers from all hospital areas. Likewise, coordination with other centers in the network is essential as it permits the sharing of experiences. The involvement of hospital management is critical for the effective introduction of health protection and promotion strategies, both in workers and in users. The raising of awareness and the ongoing training of all health workers and coordination with other health care providers in the Health network are the main aspects that require strengthening in the future.

El objetivo de este trabajo fue describir las medidas llevadas a cabo en el Hospital Germans Trias i Pujol de Barcelona, destinadas a conseguir un entorno libre de humo, así como al desarrollo de actividades de investigación, formación y abordaje clínico en relación al tabaquismo. La experiencia como centro adherido a la Red Catalana de Hospitales Sin Humo desde 2002 nos revela que para la prevención y control del tabaquismo es necesaria una agenda específica desarrollada por un Comité competente, compuesto por trabajadores de diferentes estamentos y servicios del centro. Del mismo modo, consideramos fundamental la coordinación con otros centros de la Red que permita compartir experiencias, así como la implicación de la Dirección del Centro para la implementación efectiva de las estrategias de promoción y protección de la salud, tanto en los trabajadores como en los usuarios. La sensibilización y formación continuada de todo el personal sanitario y la coordinación con otros servicios proveedores de salud de la red sanitaria se perfilan como los principales puntos a reforzar en el futuro.

El hospital como centro promotor de espacios sin humo: estrategias dirigidas al control del tabaquismo / Hospitals as promoters of smokeless spaces: strategies aimed at smoking control

El objetivo de este trabajo fue describir las medidas llevadas a cabo en el Hospital Germans Trias I Pujol de Barcelona, destinadas a conseguir un entorno libre de humo, así como al desarrollo de actividades de investigación, formación y abordaje clínico en relación al tabaquismo. La experiencia como centro adherido a la Red Catalana de Hospitales Sin Humo desde 2002 nos revela que para la prevención y control del tabaquismo es necesaria una agenda específica desarrollada por un Comité competente, compuesto por trabajadores de diferentes estamentos y servicios del centro. Del mismo modo, consideramos fundamental la coordinación con otros centros de la Red que permita compartir experiencias, así como la implicación de la Dirección del Centro para la implementación efectiva de las estrategias de promoción y protección de la salud, tanto en los trabajadores como en los usuarios. La sensibilización y formación continuada de todo el personal sanitario y la coordinación con otros servicios proveedores de salud de la red sanitaria se perfilan como los principales puntos a reforzar en el futuro

The objective of this study was to describe the measures introduced at the Hospital Germans Trias I Pujol, Barcelona, aimed at achieving a smoke-free environment, and encouraging research, training, and clinical approaches with respect to smoking. The experience gained as a center attached to the Catalan Network of Smokeless Hospitals since 2002 shows that preventing and controlling smoking requires a specific agenda developed by a competent committee comprising workers from all hospital areas. Likewise, coordination with other centers in the network is essential as it permits the sharing of experiences. The involvement of hospital management is critical for the effective introduction of health protection and promotion strategies, both in workers and in users. The raising of awareness and the ongoing training of all health workers and coordination with other health care providers in the health network are the main aspects that require strengthening in the future

Women's health 2019: Osteoporosis, breast cancer, contraception, and hormone therapy.

This review summarizes evidence that may enhance and influence clinical practice of women's health. Supporting articles were identified by reviewing high-impact medical and women's health journals published in 2017 and 2018. The chosen articles are pertinent to osteoporosis screening, hormonal contraceptive interactions with antibiotics, hormone replacement therapy in BRCA1 mutation carriers, breast cancer diagnosis using digital tomosynthesis, and risks of hormonal contraception.

Correction: Genitourinary syndrome of menopause.

In the article by A.C. Moreno, S.K. Sikka, and H.L. Thacker, Genitourinary syndrome of menopause in breast cancer survivors: Treatments are available, Cleve Clin J Med 2018; 85(10):760-766, doi:10.3949/ccjm.85a.17108, Table 2 incorrectly stated that prasterone is contraindicated in women with known or suspected breast cancer. This correction has been made online as follows. "Warning: Estrogen is a metabolite of prasterone; use of exogenous extrogen is contraindicated in women with known or suspected breast cancer; prasterone has not been studied in women with a history of breast cancer."

Genitourinary syndrome of menopause in breast cancer survivors:Treatments are available.

When treating the genitourinary syndrome of menopause (GSM) in women with breast cancer or at high risk of breast cancer, clinicians must balance the higher cancer risks associated with hormonal treatments against the severity of GSM symptoms, which can be exacerbated by breast cancer treatments. Options for patients who need hormonal therapy include locally applied estrogens, dehydroepiandrosterone (DHEA), and estrogen receptor agonists/antagonists, which vary in their impact on breast cancer risk.

The C2 domain of Tollip, a Toll-like receptor signalling regulator, exhibits broad preference for phosphoinositides.

TLRs (Toll-like receptors) provide a mechanism for host defence immune responses. Activated TLRs lead to the recruitment of adaptor proteins to their cytosolic tails, which in turn promote the activation of IRAKs (interleukin-1 receptor-associated kinases). IRAKs act upon their transcription factor targets to influence the expression of genes involved in the immune response. Tollip (Toll-interacting protein) modulates IRAK function in the TLR signalling pathway. Tollip is multimodular, with a conserved C2 domain of unknown function. We found that the Tollip C2 domain preferentially interacts with phosphoinositides, most notably with PtdIns3P (phosphatidylinositol 3-phosphate) and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate), in a Ca2+-independent manner. However, NMR analysis demonstrates that the Tollip C2 domain binds Ca2+, which may be required to target the membrane interface. NMR and lipid-protein overlay analyses suggest that PtdIns3P and PtdIns(4,5)P2 share interacting residues in the protein. Kinetic studies reveal that the C2 domain reversibly binds PtdIns3P and PtdIns(4,5)P2, with affinity values in the low micromolar range. Mutational analysis identifies key PtdIns3P- and PtdIns(4,5)P2-binding conserved basic residues in the protein. Our findings suggest that basic residues of the C2 domain mediate membrane targeting of Tollip by interaction with phosphoinositides, which contribute to the observed partition of the protein in different subcellular compartments.

Freqüência da doença periodontal em gestantes com parto pré-termo: realizada no serviço de assistência médica de Barueri - São Paulo / Frequency of periodontal disease in pregnant women with preterm

Este estudo procurou verificar a freqüência da doença periodontal em um grupo de 180 gestantes brasileiras e a provável inter-relação com o nascimento de prematuros. Durante o pré-natal os dados anamnéticos e o exame periodontal das pacientes foi realizado. Após o parto as puérperas foram recontatadas e os dados do bebê e do parto coletados e analisados estatisticamente. Estes mostraram que, o parto pré-termo ocorreu em 10% dos casos sendo que, a doença periodontal aumentou em 3,2 vezes a chance de ocorrência de prematuridade após a eliminação das variáveis de controle. Os dados foram estatisticamente significativos, p<0,05, de forma que a alta prevalência da doença periodontal obtida demonstrou forte associação com o parto pré-termo nesta população

This research aims to observe the prevalence of periodontal disease in a group of 180 pregnant Brazilian women and identify the probable correlation with preterm birth. Anamnesis and periodontal examination were performed during the pre-natalsessions. Once the baby was born, all data necessary for statistical analysis was collected. The results revealed a 10% occurrence of prematurity from the total population, and that periodontal disease increased, by 3.2 times, the chances of preterm births occurring, after the elimination of the control’s varieties. The statistic test was significant enough, p<0.05, to demonstrate strong association of preterm birth with periodontal disease

Cirurgia endoscòpica: aplicacions en pediatria / No disponible

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Etiology and outcome of community-acquired pneumonia in patients with diabetes mellitus.

STUDY OBJECTIVES: It has been suggested that diabetes mellitus is associated with an increased susceptibility to infection, the risk of using more aggressive therapeutic agents, and increased morbidity and mortality; however, current evidence supporting these events in the field of pneumonia is scarce. The aim of the present study was to provide information on clinical and microbiological characteristics and the outcome of community-acquired pneumonia in patients with diabetes mellitus. DESIGN: Prospective study of cases. SETTING: A university hospital in Lleida, Spain. PATIENTS: During a 5-year period, we prospectively studied the clinical and radiologic characteristics, the spectrum of causative agents and other microbiological data, and the outcomes of 660 consecutive episodes of community-acquired pneumonia. Data derived from 106 patients with diabetes mellitus were analyzed and compared with data obtained from the remaining population. MEASUREMENTS AND RESULTS: Patients with diabetes mellitus were significantly older (p = 0.001) and more frequently had other concomitant comorbid conditions (p = 0.018). Diabetes was also significantly associated with the development of pleural effusion (p = 0.015) and mortality (p = 0.002); for both events, diabetes remained as an independent predictive factor in multivariate analyses. By contrast, the incidence of the main etiologic agents, and the bacteremia or empyema rates did not show significant differences in relation to the remaining patients. In the subgroup of patients with diabetes, mortality was associated with the presence of multilobar infiltrates (p = 0.004), concomitant underlying diseases (p = 0.004), and some diabetes-related complications (nephropathy, p = 0.040; and vasculopathy, p = 0.002), although only multilobar infiltrates and comorbidities were selected as prognostic factors in the multivariate analysis. CONCLUSIONS: In patients with community-acquired pneumonia, diabetes mellitus is associated with a poor prognosis, increasing the rate of pleural effusion and mortality. Our results suggest that this adverse outcome is more attributable to the underlying circumstances of patients than to uncommon microbiological findings.